A Novel Frameshift Mutation in <i>SLC20A2</i> in a Korean Patient with Primary Brain Calcification, Parkinsonism and Memory Impairment.
A Novel Frameshift Mutation in <i>SLC20A2</i> in a Korean Patient with Primary Brain Calcification, Parkinsonism and Memory Impairment.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
KR · Author affiliation · country only
Department of Industrial and Environmental Engineering, Graduate School of Environment, Gachon University, Seongnam 13120, Republic of Korea.Location evidence
Seoul, KR · Author affiliation
Department of Neurology, Seoul National University College of Medicine & Clinical Neuroscience Center, Seoul National University Bundang Hospital, Seongnam 13620, Republic of Korea.Location evidence
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Original abstract
ObjectivesThe patient presented various neurological symptoms in her 50s, such as memory issues, insomnia, depression, and motor impairment. Diverse investigations were performed to identify the underlying causes on her neurological symptoms and understand her neuro- deteriorations.MethodsClinical neurological and brain imaging analyses: CT, MRI and PET were performed on the patient. Blood was drawn for the whole-exome sequencing and functional studies with biomarker for amyloid-beta oligomers and SLC20A2 protein in plasma.ResultsBrain imaging revealed calcifications in multiple regions, including the subcortical white matter, basal ganglia, thalami, and dentate nuclei. Genetic analysis revealed a c.1152_1153delCA, p.Asn384Lysfs*30 variant in SLC20A2 gene. The decreased SLC20A2 protein levels in plasma in comparison to healthy controls suggested a loss-of-function mechanism from the mutation. The patient had a positive AlzOn result, indicating an increased tendency for amyloid oligomerization and suggesting a potential indirect link between SLC20A2 and amyloid-beta pathways.ConclusionsA novel frameshift mutation, Asn384Lysfs*30, in the SLC20A2 gene was identified in a patient with Primary Brain Calcification (PBC). This mutation was located in a critical large loop region of the protein, where other similar mutations (e.g., Gly366fs89, Ser385Ilefs*70) were previously reported. These findings indicated that mutations in SLC20A2 caused the reduced protein expressions, potentially resulting PBC through haploinsufficiency.